Latest Drugwonks' Blog
CMPI president Peter Pitts’ opening remarks at the conference can be found here.
In the next audio clips, Steve Usdin of BioCentury moderates a panel discussion addressing the role of patients and manufacturers as it concerns access to pain medications.
The panelists are listed below:
Cindy Steinberg, National Director of Policy and Advocacy, US Pain Foundation
Bob Twillman, Director of Policy and Advocacy, American Academy of Pain Management
Stuart Kim, Associate General Counsel, Regulatory Affairs, Mallinckrodt Pharmaceuticals
You can listen to Cindy Steinberg’s presentation and the panel discussion moderated by Steve Usdin here.
In an interview with in-PharmaTechnologist.com, India’s Deputy Drug Controller, S. Eshwar Reddy, said some pretty honest – and frightening things about his nation’s perspective on global good manufacturing practices (GMP) – or purposeful lack thereof.
When asked if Indian manufacturers -- which produce more than 40 per cent of the API used in the US and Europe -- should be more sympathetic with Western guidelines and regulations, Reddy said the opposite should be true.
He said any additional requirements made are the sole responsibility of the authority which issues them.
“If the importing country has specific GMP requirements, that is their responsibility to audit the facilities. It is the responsibility of the importing country not the exporting country.”
Talk about passing the rupee.
“Being the Indian drug regulatory authority we don’t have any monitoring mechanism of other countries’ regulations. Each country has their own set of laws so Indian regulatory authorities don’t have any control.
So much for global regulatory fraternity.
BioCentury reports that the Generic Pharmaceutical Association has requested (via Citizen's Petition) that the FDA allow biosimilar and interchangeable biologics to use the same international non-proprietary name (INN) as reference biologics. GPhA said requiring different INNs for biosimilars and the original biologic would "inaccurately suggest that these products have meaningful clinical differences for patients."
The petition asserts that FDA lacks legal authority to require separate INNs for biosimilars. GPhA also noted that FDA has allowed originator biologics, including antihemophilic factors, to share an INN even if they differ in manufacturing method.
The agency is developing a guidance document on naming biosimilars and interchangeable biologics. According to Rachel Sherman, CDER’s Director of the Office of Medical, the naming policy will be designed to ensure that products can be tracked and traced, "Pharmacovigilance is our prime concern; we need to know who is getting what." noted Sherman.
Smart money (and savvy public health practice) predicts the petition will be denied.
Last night I attended an elegant dinner at the New York Public Library (sponsored by Johnson & Johnson and Scientific American) where the 2013 Dr. Paul Janssen Award for Biomedical Research was presented to Dr. David Julius.
Dr. Julius received the award for his role in identifying the molecular mechanisms of touch, pain, and thermosensation. A scientific slam-dunk.
The highlight of the evening wasn’t the chicken and rice pilaf – it was Dr. Julius’ speech where he highlighted the inherent tension (“not conflict”) between the translational research and “curiosity-based science.”
A bold topic in a room filled with J&J’s top brass.
And an important topic for a number of reasons, not the least of which is the steady decrease on NIH funding for academia (a trend likely to continue unless they strike oil in Bethesda) and the nascent uptick in the outsourcing of pharma R&D to ivy-covered halls.
Per Dr. J, academe and industry and Uncle Sam are going to have to find new ways not only to mutually co-exist – but also to fruitfully collaborate.
At the end of the day it’s all about encouraging innovation, both incremental and discontinuous.
(I asked Dr. Julius to send me his remarks, and when they arrive I will be sure to post them.)
On a wet and cold December 8, 2003, I sat in Constitution Hall and watched President Bush sign Part D into law. I helped (in my own small way) to make it happen. It’s something of which I’m proud.
Nearly a decade later that pride is stronger than ever. A new, nationally representative survey shows that an overwhelming nine out of 10 seniors with Medicare prescription drug coverage are satisfied.
· Ninety-seven percent report that their coverage works well, and nearly three out of four seniors say it works “very well.”
Some specifics:
Part D Reliability at Its Highest Level: Those feeling “peace of mind” by having Part D coverage reached an all-time high level of 96 percent this year, with 73 percent saying they feel a “great deal” of peace of mind and 23 percent saying they feel “some” peace of mind.
Multiple Factors Drive High Satisfaction: Of those surveyed, 95 percent say their plan is convenient to use (a six percent increase from 2006), 84 percent say both their premiums and copays are affordable, and 88 percent say that their Part D plan is meeting their expectations.
Seniors Know What to Look for in a Part D Plan: Seniors believe that a variety of factors are important when deciding on a Part D plan. Eighty-eight percent think that the co-pays or coinsurance amounts are important, 86 percent believe that identifying the pharmacies where they could use their benefit to purchase their medicines is important, and 81 percent believe that the quality ratings of the plan are important to examine.
High Satisfaction Seen across Major Demographic Groups: High satisfaction levels within African American (95 percent) and Hispanic (94 percent) constituencies, as well as within various income levels (93 percent for both those earning less than $15,000 per year or more than $50,000 per year), reinforce the overall findings of a successful program. Additionally, 92 percent of men and 89 percent of women are satisfied with their coverage.
Seniors Rely on the Program: This year, 72 percent of beneficiaries said that they’re better off now than before they had Part D coverage – a four percent increase from last year. Eighty-six percent of seniors fear that eliminating Part D would increase their out-of-pocket prescription costs, and without a plan, 62 percent say they would be forced to cut back or eliminate some prescription regimens – a nine percent increase from 2012.
Seniors Would Recommend Coverage to Others: 89 percent of Part D enrollees say they would recommend the program to someone considering Medicare enrollment.
The full survey can be found here.
Per the FDA’s import alert for drugs made in Ranbaxy's Mohali plant in northern India, the agency said it found "significant" violations of manufacturing rules, "including failure to adequately investigate manufacturing problems."
Now at least three of Ranbaxy's eight plants in India are unable to export to the U.S. Among its facilities outside of India, the Gloversville, N.Y., plant received a warning letter from the FDA in December 2009 for manufacturing violations. That facility has since been closed.
For more on this issue, see Indians and Cowboys.
Yes, Virginia. Quality counts.
Ranbaxy, the Indian generics manufacturer that recently paid half a billion dollars to settle fraud allegations and quality problems, has just received an FDA import alert against their production facility in Mohali, Punjab state.
The plant was set to make generic versions of blood-pressure pill Diovan.
Ranbaxy facilities in Dewas and Paonta Sahib, India, have both been on the FDA’s import alert list since 2009.
The relevance for more complicated products (like Gleevec) and biosimilars more broadly – is obvious.
According to Bloomberg report, the latest FDA notice “is a surprise,” said Prakash Agarwal, a health-care analyst with CIMB Securities India Pvt. Ltd. “The understanding was that, given the past experience with the two other facilities, the management would be on their toes to resolve these issues.”
Fast and loose is not an option.
TGIF. Now let’s talk about Prescription Drug Monitoring Programs (PDMP) and the intended and unintended consequences thereof.
How wide a net should PDMPs cast before they begin to have the unintended consequence of restricting legitimate patient access? Well, according the general consensus at Tuesday’s Capital Hill conference on Personalized Medicine and Responsible Access to Pain Medication, PDMPs should include Schedules 2-4. To infinity and beyond may make for good soundbites, but makes no practical sense.
What about e-standards for inter-operability with electronic health records? This point was made by Bob Twillman, of the American Academy of Pain Management. Big Data is certainly part of the answer. Knowledge is Power.
And speaking of data – what about data entry? PDMPs should allow not only pharmacists, but also physicians and their staffs to be able to enter and update electronic records. Let’s get real – this is already the reality on the ground. But this must also be matched with proper oversight for both quality control and appropriate access.
This raises the prospect of doing something that Indiana started doing with its PDMP a couple of years ago -- and that a lot of other states want to do. The Hoosier State made it possible for prescribers to communicate with other prescribers about patients—so, if prescriber B sees a patient and discovers that Prescriber A has prescribed before, B can contact A and make arrangements for which one of them is going to follow the patient. Notes also can be left behind for other providers, for instance, if an ER doc gets a doctor shopper, he can leave a note about it so others are forewarned.
What about pharmacists? What’s their role? Should they have broader access to patient data? Beyond being deputized by the DEA, the pharmacy community must be able to play a more appropriate role as a healthcare professional.
Perhaps one of the toughest issues is the role of abuse deterrent formulations (ADF). Beyond the debate over whether the FDA should insist that all generics be abuse deterrent (and the related IP debate), how should PDMPs instruct physicians and pharmacists? And what about formularies? Can we trust physicians to make the right call? Do all patients need abuse deterrent formulation? And, if not, what are the decision criteria? What about dose and duration limitations?
Or should there be state regulations per ADFs at all? Shouldn’t those decisions reside within the FDA? Can you say federal preemption?
This places both education (of the CME variety) and best practices (developed not just by PDMPs but also by physicians, pharmacists, and patient organizations) front and center. What about REMS training? And what about more precise criteria for what a “pain specialist” or a “pain clinic” even mean? As the saying goes, “if you can’t measure it, then it doesn’t count.”
What about take-back programs? Should they only be limited to opioids? And who should pay for them?
Lastly, amercement. On a state-by-state level, does the punishment fit the crime? Should there be national standards on criminal and civil penalties?
Many tough questions – but they deserve thoughtful and timely answers. It’s time for a focused national dialogue that recognizes the need for effective oversight through the use of Big Data and broader constituent alliances.
The conventional view serves to protect us from the painful job of thinking.
-- John Kenneth Galbraith
Pierre Trudeau once said, “There's no place for the state in the bedrooms of the nation.“ But what’s the appropriate place for the state in our nation’s pharmacies and medicine chests – particularly for opioids?
Yesterday was the day to address that question.
First there was the FDA’s announcement of class-wide labeling changes and new post-market study requirements for extended-release and long-acting opioids.
Until now, the FDA had said the drugs were appropriate for the treatment of "moderate-to-severe" pain. The new drug label drops the word "moderate" and says it should be used only to manage "pain severe enough to require daily, around-the clock, long-term treatment." Additionally, FDA is adding a boxed warning on the risk of neonatal opioid withdrawal syndrome.
The agency said manufacturers must conduct one or more post-marketing studies to quantitatively estimate the risks of misuse, abuse, addiction, overdose and death associated with long-term use, as well as a clinical trial to evaluate the risk of developing increased sensitivity to pain with long-term use of extended-release and long-acting opioids. Companies also must conduct a study of "doctor/pharmacy shopping" -- a practice in which patients visit multiple doctors and pharmacies to obtain prescriptions -- and whether it is "suggestive of misuse, abuse and/or addiction." Per a report in BioCentury, “FDA said companies should work together on the post-marketing studies.”
Once the labeling changes are finalized, FDA said it will modify the classwide REMS for extended-release and long-acting opioids. The REMS, which the agency approved in 2012, requires companies to make educational programs available to prescribers at no or nominal cost but does not require prescribers to participate and does not include a prescriber registry.
The other big new was a Capital Hill conference on Personalized Medicine and Responsible Access to Pain Medication (sponsored by the Center for Medicine in the Public Interest – the think tank home of drugwonks.com). I was honored to chair the event.
Speakers included Bob Twillman of the American Academy of Pain Management, Cindy Steinberg of the US Pain Foundation, Stuart Kim of Mallinckrodt Pharmaceuticals, Steve Usdin of BioCentury, syndicated healthcare columnist Judy Foreman, and Professor Charles Inturrisi of Weill Cornell Medical Center.
The speakers and attendees rocked the Rayburn Building. Video of the event will soon be posted on the CMPI website.
I tried to set the tone with my opening comments:
Joshua Lederberg, the Nobel Prize Laureate once observed that the failure of regulatory, legal and political institutions to integrate scientific advances into risk selection and assessment was the most important barrier to improved public health.
Lederberg noted that in the absence of such changes, "the precedents affecting the long-term rationale of social policy will be set, not on the basis of well-debated principles, but on the accidents of the first advertised examples."
Policies and regulations that seek to limit risk are often shaped by the immediate fear of sensational events. This perspective is commonly called "The Precautionary Principle" which in various forms asserts that unless innovators can demonstrate that a new technology is risk free, it should be not allowed into the marketplace. Moreover, any product that could possibly be dangerous at any level should be strictly and severely regulated.
But precaution is not always safer than the alternatives.
Some current examples of precaution and the public health
· The National Action Plan for Adverse Drug Event Prevention, just announced in a Sept. 4 Federal Register notice, outlines a comprehensive strategy to reduce AEDs for opioids. Much of the research actions called for by the plan seem designed to decrease prescribing. For instance, the plan calls for research by CDC, NIH and, public-private collaborations to look into adopting adjunctive and behavioral modalities to augment and reduce opioids use for chronic pain;
· Upscheduling and the relabeling of medicines to treat depression, diabetes, chronic and acute pain;
· And, finally, the role of tamper-resistant technologies in the appropriate management of pain medicines (both innovator and generic).
It’s also important to consider the DEA’s “Thug Regulation” strategy that results in a decline in appropriate patient access; an increase in regulatory time and cost and, ultimately, a decline in innovation.
The California Medical Association has received reports from physicians that Walgreens pharmacists are refusing to fill controlled substances prescriptions without additional information from the prescriber.
Per dictates from the DEA, Walgreen’s pharmacists are now demanding that physicians provide information on diagnosis, ICD-9 codes, expected length of therapy and previous medications tried and failed.
In other words, tighter restrictions for patients who really need the medications, more paperwork for physicians and a heavier workload for pharmacists. Abusers and criminals rarely follow regulations.
When you have a hammer, every problem looks like a nail. The DEA sees opioid abuse and seeks to minimize access to them. That’s a law enforcement solution. They mean well – but are behaving like a bull in a china shop
Arbitrarily limiting choice is not generally associated with the Scientific Method.
Should regulation be shaped by factors other than science or should advances in medicine and digital information be used to right-size regulation, reduce the excessive reductionism that leads to regulatory overreaction and promote resilience rather than ever increasing restrictions?
Consider the program recently instituted by CVS (and detailed in a recent New England Journal of Medicine Perspective piece) where, via the use of “Big Data” the chain pharmacy identified “outlier prescribers” and took appropriate and responsible actions.
The DEA’s attempt to deputize pharmacists on the one hand and the CVS program on the other raise some interesting questions:
· What will the role of the 21st century pharmacist be in improving drug safety and medication adherence via more proactive (and remunerated) patient education?
· How can pharmacists become better integrated (beyond Med Guides) into the FDA’s Safe Use of Medicines initiative?
· When will pharmacy synchronization programs really kick into gear, and how will states help to jump-start these important initiatives?
To paraphrase the American political scientist Aaron Wildavsky, we at the Center for Medicine in the Public interest believe in a strategy of resilience based on experience. We must learn from adverse consequences in order to develop a capacity to advance the public health. Variability is the key to survival.
THANK YOU.
Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.
